全文获取类型
收费全文 | 137篇 |
免费 | 4篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 1篇 |
妇产科学 | 3篇 |
基础医学 | 26篇 |
口腔科学 | 1篇 |
临床医学 | 4篇 |
内科学 | 28篇 |
皮肤病学 | 2篇 |
神经病学 | 6篇 |
外科学 | 12篇 |
综合类 | 17篇 |
眼科学 | 4篇 |
药学 | 16篇 |
中国医学 | 4篇 |
肿瘤学 | 21篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 5篇 |
2013年 | 13篇 |
2012年 | 11篇 |
2011年 | 13篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 9篇 |
2007年 | 8篇 |
2006年 | 10篇 |
2005年 | 11篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 1篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
排序方式: 共有147条查询结果,搜索用时 78 毫秒
41.
Angenete E Langenskiöld M Palmgren I Falk P Oresland T Ivarsson ML 《International journal of colorectal disease》2007,22(11):1331-1338
Background Rectal cancer patients are treated with surgery and sometimes radiotherapy. Transforming growth factor-β1 (TGF-β1) acts both
as an inhibitor of tumour growth and as a promoter of tumour progression. The aim of this study was to determine the levels
of TGF-β1 in tumour tissue, adjacent mucosa and plasma in rectal cancer patients and relate these to the effect of radiotherapy
and clinical outcome.
Materials and methods One hundred and ten patients scheduled for rectal cancer surgery were included, 49% received pre-operative radiotherapy three-field
treatment 5 × 5 Gy. Blood samples and biopsies were taken during surgery and later assayed with enzyme-linked immunosorbent
assay for total TGF-β1 and active TGF-β1. Patients were then followed for 3 years.
Results Total and active TGF-β1 was higher in tumour tissue compared with rectal mucosa (p < 0.0001). Active TGF-β1 in tumour tissue and rectal mucosa was lower in the irradiated group (p = 0.007; p < 0.0001). Total TGF-β1 was higher in patients with metastases at primary diagnosis (p = 0.005) compared to patients without. In patients who later developed metastases, the levels of active TGF-β1 in plasma
were lower (p = 0.004). Local recurrence was associated with lower levels of total TGF-β1 in the rectal mucosa (p = 0.038).
Conclusions Higher levels of total TGF-β1 in tumour tissue at surgery may be indicative of distant metastases, and low levels of active
TGF-β1 in plasma may indicate a risk of developing secondary metastases. Lower levels of total TGF-β1 in rectal mucosa may
influence risk of local recurrence. Measurement of TGF-β1 in rectal cancer patients may be of clinical use in the future. 相似文献
42.
New aspects in celiac disease 总被引:8,自引:2,他引:6
Celiac disease (CD) is a common autoimmune disorder characterized by an immune response to ingested gluten and has a strong HLA association with HLA- DQ2 and HLA-DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic susceptibility to gluten intolerance. CD is caused by the lack of immune tolerance (oral tolerance) to wheat gluten. In this sense, the expression of soluble HLA-G in CD is of special interest because the molecule plays an important role in the induction of immune tolerance. The enhanced expression of soluble HLA-G found in CD may be part of a mechanism to restore the gluten intolerance. In this editorial, we review recent progress in understanding CD in relation to its prevalence, diagnosis and possible mechanisms of pathogenesis. 相似文献
43.
To investigate the molecular mechanism by which Tanshinone Ⅱ A (TSN Ⅱ A) prevents left ventricular hypertrophy (LVH), we examined the expression of AT1R, TGF-β1 and Smads gene in the hypertrophic myocardium of hypertensive rats with abdominal aorta constriction. LVH model was established by creating abdominal aorta constriction. Four weeks later, animals were randomly divided into 4 groups with 8 animals in each. One group was used as model control, the other three groups were treated with TSN ⅡA (20 mg/kg), TSN ⅡA (10 mg/kg) and valsartan (10 mg/kg), respectively. Another 8 SD rats were subjected to sham surgery and served as blank control. After 8- week treatment, the caudal artery pressure of the animals was measured. The tissues of left ventricle were taken for the measurement of the left ventricular mass index (LVMI) and pathological sectioning and HE-staining were used for determining the myocardial fiber dimension (MFD). The mRNA expression of AT1R, protein expression of TGF-betal and activity of Smad-2, 4, 7 were detected by RT-PCR and Western blotting, respectively. Our results showed that (1) the blood pressure of rats treated with TSN Ⅱ A, either at high or low dose, was significantly higher than those in the control and valsartan-treated group (P〈0.01, P〈0.05); (2) LVMI and MFD in TSN Ⅱ A and valsartan-treated rats were higher than those in the control group (P〈0.05) but significantly lower than those in the model control (P〈0.01); (3) the high doses of TSN Ⅱ A and valsartan significantly down-regulated the mRNA expression of AT 1R and protein expression of TGF-beta l and Smad-3 in the hypertrophic myocardium (P〈0.01), and TGF-betal in valsartan-treated animals was more significantly lower than that in rats treated with TSN Ⅱ A; (4) the two doses of TSN Ⅱ A and valsartan significantly up-regulated the protein expression of Smad-7 in the hypertrophic myocardium (P〈0.01), and Smad-7 in the animals treated with high-dose TSN Ⅱ A was significantly higher than that in rats treated with valsartan. It is concluded that inhibition of myocardial hypertrophy induced by TSN ⅡA independent of blood pressure. The underlying mechanism might be the down-regulated expression of AT1R mRNA and Smad-3, increased production of Smad-7, and blocking effect of TSN Ⅱ A on TGF betal/Smads signal pathway in local myocardium. 相似文献
44.
Yingzi Cong Ting Feng Kohtaro Fujihashi Trenton R. Schoeb Charles O. Elson 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(46):19256-19261
A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4+CD25+ Tregs decreased IgA+ B cells, total IgA, and CBir1-specific IgA in gut within days. Repletion of T cell-deficient mice with either CD4+CD25+ or CD4+foxp3+ Tregs restored intestinal IgA to a much greater extent than their reciprocal CD4+ subsets, indicating that Tregs are the major helper cells for IgA responses to microbiota antigens such as flagellin. We propose that the major role of this coordinated Treg-IgA response is to maintain commensalism with the microbiota. 相似文献
45.
Hereditary haemorrhagic telangiectasia, inherited as an autosomal dominant trait, affects approximately 1 in 5000 people. The abnormal vascular structures in HHT result from mutations in genes (most commonly endoglin or ACVRL1) whose protein products influence TGF-ß superfamily signalling in vascular endothelial cells. The cellular mechanisms underlying the generation of HHT telangiectasia and arteriovenous malformations are being unravelled, with recent data focussing on a defective response to angiogenic stimuli in particular settings. For affected individuals, there is often substantial morbidity due to sustained and repeated haemorrhages from telangiectasia in the nose and gut. Particular haematological clinical challenges include the management of severe iron deficiency anaemia; handling the intricate balance of antiplatelet or anticoagulants for HHT patients in whom there are often compelling clinical reasons to use such agents; and evaluation of apparently attractive experimental therapies promoted in high profile publications when guidelines and reviews are quickly superseded. There is also a need for sound screening programmes for silent arteriovenous malformations. These occur commonly in the pulmonary, cerebral, and hepatic circulations, may haemorrhage, but predominantly result in more complex pathophysiology due to consequences of defective endothelium, or shunts that bypass specific capillary beds. This review will focus on the new evidence and concepts in this complex and fascinating condition, placing these in context for both clinicians and scientists, with a particular emphasis on haematological settings. 相似文献
46.
47.
目的 观察转化生长因子-β(TGF-β)受体抑制剂复合物 C对人胚胎干细胞(hESC)向视网膜色素上皮(RPE)细胞定向诱导效率的影响。方法 将H1 hESC分为对照组和实验组。对照组在细胞过度融合后,以去除碱性成纤维细胞生长因子的血清替代物培养体系诱导RPE细胞定向分化。实验组于诱导分化前6 d在培养体系中加入1 μmol/L 复合物 C。诱导分化第1、3、5周,采用实时荧光定量逆转录聚合酶链反应(RT-PCR)检测两组人类配对盒基因(PAX6)、小眼球相关转录因子(MITF)、细胞视黄醛结合蛋白(CRALBP)、RPE65 mRNA的表达。将hESC来源的RPE(hESC-RPE)细胞分离纯化,采用RT-PCR、蛋白免疫印迹法(Western blot)和细胞免疫荧光法对纯化的hESC-RPE细胞进行鉴定。结果 诱导分化第4周,实验组肉眼可见色素团块,对照组无色素团块出现。将实验组的色素细胞分离纯化后,可见100%的细胞表现为多角形色素化。RT-PCR检测结果显示,实验组PAX6 mRNA表达在诱导分化第1、3周显著高于对照组,差异有统计学意义(t=28.498、3.141,P<0.05);诱导分化第3、5周,实验组MITF(t=8.866、10.111)、CRALBP(t=5.293、5.394)和RPE65(t=9.263、9.504)的表达均明显高于对照组,差异有统计学意义(P<0.05)。hESC-RPE细胞PAX6、MITF、CRALBP、RPE65 mRNA表达均显著高于hESC(t=9.154、17.284、18.204、44.194)和ARPE-19(t=7.605、16.770、18.190、44.190)细胞,差异有统计学意义(P<0.05)。Western blot检测结果显示,hESC-RPE细胞高水平表达RPE标志蛋白PAX6、RPE65。荧光显微镜观察发现,hESC-RPE细胞表达RPE细胞特异性标志蛋白PAX6、紧密连接蛋白-1。结论 TGF-β受体抑制剂复合物C能显著提高hESC向RPE定向诱导效率。 相似文献
48.
Christopher Larson Bryan Oronsky Nacer E Abrouk Arnold Oronsky Tony R Reid 《American journal of cancer research》2021,11(10):5184
Transgene-enhanced oncolytic adenoviruses represent a promising novel therapeutic option for the treatment of cancer. A Phase 1 clinical trial featuring AdAPT-001 is ongoing (). AdAPT-001, a type 5 adenovirus, which carries a TGF-β trap transgene that neutralizes the immunosuppressive cytokine, TGF-β, has been shown in an immunocompetent mouse model to eradicate both locally injected and non-injected tumors. Single dose biodistribution of the TGF-β trap transgene was also evaluated in tumor bearing mice, providing an explanation for systemic activity. The biodistribution and toxicity of a single administration of mouse AdAPT-001 (mAdAPT-001) in 129S1 immunocompetent mice bearing ADS-12 tumors (mouse lung carcinoma) were assessed. mAdAPT-001 was injected intratumorally and intravenously in groups of 25 mice each at varying dose levels. Soluble TGF-β trap was detected in the serum using ELISA. A single AdAPT-001 injection resulted in non-negligible long-term TGF-β trap persistence in the serum over the 14-day study after intravenous and intratumoral administration. No TGF-β-related toxicity was observed. At clinically relevant doses, AdAPT-001 was safe and well tolerated. Systemic levels of the TGF-β trap transgene were observed from both local and intravenous dosing. NCT04673942相似文献
49.
New advancements have been made in recent years in the understanding of the molecular mechanisms that govern human liver tumorigenesis.
Experimental animal models have been widely used, especially mouse models. In this review we highlight some of the genetically
engineered mouse models that have proved to be excellent tools to study the intracellular signalling pathways altered in hepatocarcinogenesis
and establish potential correlations with data from humans, with special focus on hepatocellular carcinoma (HCC), the most
common type of primary liver cancer. Information obtained from these animal models will help to design future therapeutic
approaches to HCC, particularly those that explore drugs that specifically target the altered molecular pathways.
Supported by an unrestricted educational grant from Merck Serono 相似文献
50.
Therapeutic Targets in the Treatment of Allograft Fibrosis 总被引:4,自引:4,他引:0
R. B. Mannon 《American journal of transplantation》2006,6(5P1):867-875
The dramatic improvements in short-term graft survival and acute rejection rates could only have been dreamed of 20 years ago. Late graft loss following kidney transplantation is now the critical issue of this decade. Frequently, graft loss is associated with the development of tubular atrophy and interstitial fibrosis within the kidney (i.e. chronic allograft nephropathy; CAN). Major treatment strategies in this disorder are non-specific and the focus of intervention has been on limiting injurious events. Following graft injury is a fibrogenesis phase featuring both proliferative and infiltrative responses mediated by chemokines, cytokines and growth factors. In particular, TGFβ has been strongly implicated in the pathogenesis of chronic injury and epithelial-mesenchymal transformation (EMT) may be part of this process. The cascade of events results in matrix accumulation, due to either increased production and/or reduced degradation of matrix. Recent investigations into the pathogenesis of tissue fibrosis have suggested a number of new strategies to ameliorate matrix synthesis. While the majority of therapies have focused on TGFβ, this may not be an ideal maneuver in transplant settings and alternative targets identified in other fibrotic diseases will be discussed. Attacking graft fibrosis should be a new focus in organ transplantation. 相似文献